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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05086315




Registration number
NCT05086315
Ethics application status
Date submitted
19/10/2021
Date registered
20/10/2021

Titles & IDs
Public title
First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Scientific title
An Open-label, First-in-human, Dose-escalation/Expansion Study of SAR443579 Administered as Single Agent by Intravenous Infusion in Adult and Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Secondary ID [1] 0 0
U1111-1266-7399
Secondary ID [2] 0 0
TCD17197
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphocytic Leukaemia 0 0
Acute Myeloid Leukaemia Refractory 0 0
Myelodysplastic Syndromes 0 0
Blastic Plasmacytoid Dendritic Cell Neoplasia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR443579

Experimental: SAR443579 - Dose Escalation: SAR443579 administered intravenously at escalating dose levels.

Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.


Treatment: Drugs: SAR443579
Powder for solution for infusion; by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose-limiting toxicity (DLT) (Escalation Part)
Timepoint [1] 0 0
Day 1 to Day 28
Primary outcome [2] 0 0
Proportion of participants who have a CR (Complete Remission) + CRi (Complete Remission with Incomplete Hematological Recovery) (Expansion Part)
Timepoint [2] 0 0
Up to 6 months
Secondary outcome [1] 0 0
Recommended Dose for Expansion (RDE)
Timepoint [1] 0 0
Up to 12 months
Secondary outcome [2] 0 0
Number of participants with treatment-emergent adverse events (TEAEs) (Escalation and Expansion Parts)
Timepoint [2] 0 0
Up to 30 months
Secondary outcome [3] 0 0
Cmax: Maximum observed concentration
Timepoint [3] 0 0
Day 1 to end of trial (maximum up to 30 months)
Secondary outcome [4] 0 0
Incidence of anti-drug antibody (ADA) (Escalation and Expansion Parts)
Timepoint [4] 0 0
Up to 30 months
Secondary outcome [5] 0 0
Anti-leukemic activity as define by International Working Group (IWG) for AML (modified) and MDS, or National Comprehensive Cancer Network (NCCN) for B-ALL (Escalation Part)
Timepoint [5] 0 0
Up to 6 months
Secondary outcome [6] 0 0
Proportion of participants with CR + complete remission with partial hematological recovery (CRh) (Expansion Part)
Timepoint [6] 0 0
Up to 6 months
Secondary outcome [7] 0 0
Rate of CR + CRh + CRi + morphological leukemia-free state (MLFS) (Expansion Part)
Timepoint [7] 0 0
Up to 6 months
Secondary outcome [8] 0 0
Time interval from first documented evidence of Composite Complete Remission (CRc: (CR or CRi)) until disease relapse as per modified IWG or death due to any cause, whichever comes first (Expansion Part)
Timepoint [8] 0 0
Up to 30 months
Secondary outcome [9] 0 0
Time from the first documented evidence of CR or CRh until disease relapse or death due to any cause, whichever comes first (Expansion Part)
Timepoint [9] 0 0
Up to 30 months
Secondary outcome [10] 0 0
Time from the first documented evidence of CR or CRi or CRh or MLFS until disease relapse or death due to any cause, whichever comes first (Expansion Part)
Timepoint [10] 0 0
Up to 30 months
Secondary outcome [11] 0 0
Time interval from the first SAR443579 administration to the date of earliest evidence of relapse, treatment failure, or death (Expansion Part)
Timepoint [11] 0 0
Up to 30 months
Secondary outcome [12] 0 0
Proportion of survivors from the first SAR443579 administration to death from any cause (Expansion Part)
Timepoint [12] 0 0
Up to 12 months
Secondary outcome [13] 0 0
Rate of hematopoietic stem cell transplantation (HSCT) through SAR443579 treatment but before subsequent therapy (Expansion Part)
Timepoint [13] 0 0
Up to 30 months
Secondary outcome [14] 0 0
Time from first SAR443579 administration to discontinuation for any reason excluding remission, ie, disease progression/disease relapse, treatment toxicity, participant preference or death (Expansion Part)
Timepoint [14] 0 0
Up to 30 months
Secondary outcome [15] 0 0
Time from first SAR443579 administration to death due to any cause
Timepoint [15] 0 0
Up to 30 months

Eligibility
Key inclusion criteria
- Participant must be at least 1 year old at the time the trial participant or legal guardian signs the informed consent form and will be assigned as follows:

* Adult arm: aged at least 12 years old.
* Pediatric arm: aged 1 to 17 years old.

For participants of the Escalation Part only:

- Adult and Pediatric Arms: Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML)] according to World Health Organization (WHO) 2022 classification. Participants with AML must meet one of the following criteria, a), b), c) or d) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii.

i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.

Examples include but are not limited to:

* One cycle of high dose cytarabine (HiDAC) containing regimen
* One cycle of liposomal cytarabine and daunorubicin
* Two cycles of standard dose cytarabine containing regimen

ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2: 1. 4 cycles of hypomethylating agents (HMA) or 2. 2 cycles HMA + venetoclax

b) Early relapse (ER) AML, defined as AML in relapse with CR duration < 6 months on prior induction treatment

c) Leukemia in first or higher relapse

d) For participants aged 1 to 17 years old, primary induction failure is defined as disease refractory after two cycles of induction therapy.

* Adult arm only: Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.

* Not eligible for induction therapy and having completed =2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.
* Not eligible for autologous stem cell transplant (ASCT) and having completed =1 course of induction therapy.
* Adult and Pediatric arms and escalation part only: Confirmed diagnosis of CD123+ B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit.

For Participants in the Expansion Part Only (Adults only):

* For participants in Cohort A: Participants meeting inclusion criteria for AML participants that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
* For participants in Cohort B: Participants meeting inclusion criteria for AML participants that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
* Body weight at least 10 kg.
* Pediatric arm and escalation part only: Confirmed diagnosis of BPDCN according to World Health Organization (WHO) 2022 classification, who have relapsed or refractory disease with no available (or are ineligible) therapy with known clinical benefit.
* Pediatric arm and expansion part only: For participants in Cohort C: Participants with AML who have relapsed according to inclusion criteria for AML or have recurrent disease resistant or intolerant to available therapies.
Minimum age
1 Year
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status >2 (=18 years-old). Karnovsky Scale (16-17 years-old) <50% or Lansky Scale (<16 years-old) <50%.
* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires or required treatment with systemic immunosuppressive treatments, which may suggest a risk for immune-related adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
* History of an invasive malignancy that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
* Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology. Except for participants aged 1 to 17 years, central nervous system 1 disease (CNS1) and CNS2 disease are allowed.
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
* Prior treatment with an anti-CD123-directed agent (except for participants with BPDCN in the pediatric arm).
* Prior HSCT with relapse beyond 3 months or prior CAR-T therapy in B-ALL with relapse beyond 2 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of graft-versus-host disease (GVHD).
* Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the equivalent,
* AML, BPDCN, or HR-MDS participants with prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK). Prior CAR-T therapy is allowed for participants with B-ALL.
* Concurrent treatment with other investigational drugs.
* Radiotherapy, even if palliative in intent, may not be given during the study.
* Prophylactic use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin) during the DLT observation period in the Dose Escalation Part only. - Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
* Pregnant and breast-feeding women.
* History of solid organ transplant, including corneal transplant.
* Average QTc (using the Fridericia correction calculation) greater than 470 milliseconds (msec) at screening. For pediatric arm participants only, inadequate ejection fraction as per institutional standards at screening or any clinically significant cardiac conditions (including but not limited to congestive heart failure, myocarditis, pericarditis, arrythmias).
* Pediatric arm only: Participants with known inherited bone marrow failure syndromes (e.g., bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome). Participants with Down syndrome with adequate organ function as per Investigator discretion are allowed to participate in the study.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/11/2026
Actual
Sample size
Target
126
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Investigational Site Number :0360002 - Melbourne
Recruitment hospital [2] 0 0
Investigational Site Number :0360001 - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
China
State/province [10] 0 0
Tianjin
Country [11] 0 0
China
State/province [11] 0 0
Zhengzhou
Country [12] 0 0
France
State/province [12] 0 0
Marseille
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Netherlands
State/province [15] 0 0
Amsterdam
Country [16] 0 0
Netherlands
State/province [16] 0 0
Groningen
Country [17] 0 0
Netherlands
State/province [17] 0 0
Nijmegen
Country [18] 0 0
Netherlands
State/province [18] 0 0
Rotterdam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Utrecht

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05086315